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Alpha-GPC

Overview and Summary

Alpha GPC is a naturally occurring choline intermediary that is formed when the body breaks down cell membranes for choline. As a supplement Alpha GPC is a highly bio available form of choline that crosses the blood brain barrier and raises brain levels of choline. Inside the brain choline supports cell membrane and neurotransmitter synthesis. Of all the supplemental forms of choline, GPC is probably the most cholinergic per gram, as it’s 40% choline by weight and appears to be well absorbed.

All of the available research is discussed below, a summary of the research finds that GPC is able to:

Other Names

Important Information

Dosing

1200mg daily (3 doses 400mg) has been administered in clinical trials to relieve cognitive decline in patients with dementia (5). This dose was also able to prevent scopolamine related amnesia in healthy young humans (15)

For nootropic purposes, 300mg taken once or twice per day seems a reasonable starting point.

Relevant Articles

Absorption

GPC appears to be mostly hydrolysed (broken down) in the gut via phosphodiesterase into various metabolites such as glycerophosphate, choline and phosphorylcholine. One study in rodents using radiolabeled Alpha GPC showed various choline metabolites to be formed following oral administration (1). The authors remarked in the discussion that each of these metabolites likely have their own abortion, tissue distribution and elimination profiles.

In contrast to this, another rodent study showed that intraperitoneal injection of GPC was able to reduce age related decreases in acetylcholine receptors whereas GPC metabolites (glycerophosphate, choline and phosphorylcholine) were not able to do the same. (2)

Since it’s known that Alpha GPC can cross the blood brain barrier intact (1), and that GPC is superior to choline in improving clinical symptoms (3), it’s reasonable to assume that some of an oral dose is absorbed intact and crosses the blood brain barrier.

Looking at the research there’s no clear study in humans that shows GPC by mouth goes straight into the brain, but empirically we know that GPC is superior to lecithin derived choline at improving cognitive function. We also know that GPC in rodents can cross the BBB and that its metabolites are inferior to the whole molecule. From this it’s safe to assume some oral GPC is absorbed intact and crosses the BBB in humans.

Benefits of Alpha GPC

Memory and Learning

Active avoidance is where rodents are subjected to a small shock following a stimulus, such as a sound playing. The rats are typically presented with an escape compartment to avoid the shock. The quicker the rats learn that the sound = incoming shock, the better it performs. Administration of GPC increased the number of times the rats avoided shock and also decreased the latency, i.e. the time it took them to do so.

Another rodent study showed GPC was able to reduce the amnesiac effects of scopolamine, a potent anticholinergic drug. Its hypothesised GPC did so by increasing acetylcholine synthesis. (7)

In humans two trials have shown GPC is able to reduce scopolamine induced cognitive deficits in young healthy volunteers. (15)(16) Interestingly, GPC was unable to protect against benzodiazepine induced amnesia, supporting the idea that GPC’s cognitive enhancement effects are mediated through acetylcholine synthesis and cholinergic mechanisms.

GPC appears to be prevent the amnesiac effects that typically occur when scopolamine (a potent anti-cholinergic) is administered. Currently the two human trials aren’t available online, though both are discussed vicariously through reference 16. Perhaps the key take home point was that GPC was able to increase cognitive function above baseline for young healthy subjects, a “holy grail” of any nootropic.

Cognitive Decline (Alzheimer’s and Dementia)

A large meta-analysis involving 1570 patients across 10 clinical studies concluded that GPC significantly improves patient conditions, as assessed by mini mental state examination (MMSE) and sandoz clinical assessment geriatric scale (SGAG) (5)(9)(14). Both MMSE and SCAG are frequently used to assess cognitive impairment in patients with dementia.

Muscular Power and Growth Hormone

One small pilot study involving 7 men showed increased peak force output in the bench by 14% following ingestion of 600mg Alpha GPC (4). The study also noted a significant elevation in growth hormone.

A second study involving 8 males showed 1000mg of Alpha GPC was able to significantly increase growth hormone and markers of fat oxidation (8)

Alpha GPC’s Mechanism Of Action

Cell Membrane Synthesis and Maintenance

Alpha GPC increases brain choline content. As choline is a required building block for cell membranes it’s no surprise that Alpha GPC supports cell membrane upkeep by increasing the brain’s supply of choline.

Research involving young and aged rats showed chronic treatment of GPC (200mg/KG) was able to restore muscarinic receptor density (specifically M1) to youthful levels in both the hippocampus and striatum (2). A similar study also found GPC was able to partially restore M1 muscarinic density to youthful levels. (10)

Research also indicates GPC is partially able to restore cell membrane fluidty (in part) to youthful levels in the striatum and hippocampus. (10)

Neurotransmitter Synthesis

Alpha GPC produced when cell membranes are taken apart for their choline content, a process known as auto cannibalisation (18)(19). It’s no stretch then, that oral GPC supplements support acetylcholine synthesis by providing the brain with the raw materials.

Increasing Cholinergic Transporters

A seven day treatment of 150mg/kg a day Alpha-GPC found GPC increased frontal cortex acetylcholine concentration. The research indicated that cholinergic transporters VAChT (Vesicular acertylcholine transporter) and ChAT (choline acetyltransferase) were significantly expressed more in both the striatum and cerebellum following GPC. (11) Further research showed 100mg/KG GPC restored AhCE (acetylcholinesterase) to more youthful levels in aged rats. (12)

Supporting Acetylcholine Synthesis

4 studies in total have been conducted with GPC and the anticholinergic drug scopolamine. Two involving rodents showed GPC was able to prevent scopolamine induced amnesia by supporting acetycholine synthesis (7)(13)

A study involving 32 healthy human volunteers showed 10 day pre-treatment with GPC was superior to placebo at blocking the negative cognitive effects of scopolamine. The dosage used was 1200mg per day. Specifically GPC was able to help maintain attention scores and improve word recall. Interestingly GPC improved baseline performance for the word recall test, suggesting cognitive enhancement in young healthy individuals (15). (Full paper unavailable online, though abstract available and paper is discussed here (http://www.ncbi.nlm.nih.gov/pubmed/23387341)

The same researchers conducted a second study involving 48 young men and women. Volunteers were pre-treated with either; GPC (1200mg/Day), idebenone or aniracetam for 7 days. Cognitive performance, particularly in verbal memory and working memory was significantly protected by GPC. Alpha-GPC was found to be superior to aniracetam and idebenone in these respects. (Full paper unavailable online, paper is discussed in ref 16)

Safety and Side Effects

GPC appears to be a remarkably safe nootropic that processes few-little side effects in the therapeutic dose range. One trial reported side effects in 2.4% of all patients, which consisted by mainly of nausea (0.5%), heartburn (0.7%) and insomnia (0.4%) at a dose of 1200mg/day. (17)

The LD50 for GPC is 10,000mg / Kilo for rodents when administered orally. A drop in food consumption and increase in bodyweight was noted in rodents at a dose of 1000mg/kg. (17)